Effect Of Ischemia/Reperfusion On Membrane Ionic Channels Of Rat Ventricular Myocytes

Objective:The reperfusion arrthymias is one of the important aspects on ischemia-reperfusion injury, especially arrhythmogenesis.Ventricular electrical activities base on membrane ionic channels. The channels' varieties take pivotal effect in the arrthymias after reperfusion. In order to explore the ionic mechanism of the arrhythmias during ischemia- reperfusion, the present studies were undertaken to investigate the changes of sodium current (INa)and transient outward k+ current (Ito)after ischemia-reperfusion.Methods:Forty rats (300 to 350g) were used in these studies. Reinfused models were made in routine method. Single ventricular myocytes were enzymatically isolated from rat hearts reinfused after 10 and 30 minutes'myocardial ischemia .The cardiac inward sodium current (INa)and transient outward k+ current (Ito)were investigated using the whole-cell patch-clamp method in single myocyte enzymatically isolated from rat ventricle.Results1 The maximal peaks of INa from cells in the reinfused after 10 minutes' ischemia group were significantly decreased to -6.51±1.06 PA/PF(n=10cells),compared to cells from control group(-13.55±2.33)PA/PF(n=12cells), P<0.01.While the maximal peaks of INa from cells in the reinfused after 30 minutes' ischemia group were significantly increased to -41.27±4.43 PA/PF(n=10cells), compared to cells from control group, P<0.01.The steady-state inactivation curve was shifted to the hyperpolarizing direction in the reinfused after 10 minutes' ischemia group and to the depolarizing direction in the reinfused after 30 minutes' ischemia group, the half-maximal voltage dependence of inactivation (V1/2) was -112±5.6mV in the reinfused after 10 minutes' ischemia group, -101±6.2mV in the reinfused after 30 minutes' ischemia group and -105±5.3mV in the control group.Respectivity time course of recovery of INa from inactivation was faster in the control group than the reinfused after 10 minutes' ischemia group and after 30 minutes' ischemia group. There are significantly difference of the recovery degree between the control group and the reinfused after 10 minutes' ischemia group.2 The maximal peaks of Ito were significantly decreased from 52.16±5.24 PA/PF in control to 7.24±1.16 PA/PF and 6.44±1.24 PA/PF in the reinfused after 10 minutes' ischemia group and after 30 minutes' ischemia group respectively. There are significantly discrepancy among three groups. The steady-state inactivation curve was shifted to the depolarizing direction both in the reinfused after 10 minutes' and 30 minutes' ischemia groups. The half-maximal voltage dependence of inactivation (V1/2) was significantly reduced from -87.5±6.3mV in control to-68.9±5.4mV and -67.6±5.7mV the reinfused after 10 minutes' and 30 minutes' ischemia groups respectively. There weren't significantly difference of the recovery degree and time course of recovery of Ito from inactivation among three groups. Conclusions 1 The present showed that the diversification of membrane ionic channel caused by ischemia-reperfusion, further more the electrophysiologic abnormality resulted from its corresponding changes of membrane ionic current during ischemia-reperfusion. INa was Inhibitated in the reinfused after 10 minutes' ischemia groups and activated in the reinfused after 30 minutes' ischemia groups. Inhibitation of Ito was found both in the reinfused after 10 minutes' and 30 minutes' ischemia groups. Inhibitation of INa and Ito might make accountable for generating arrthymias. Activation of INa in the reinfused after 30 minutes' ischemia groups might be one of the reasons for the calcium overloading,which could lead to spring activity and generate arrthymias. 2 It is important to study the myocardioelectrophysiology and physiology during ischemia-reperfusion. However, it is insufficient, especially in cardiothoraic surgical field. So far it is available that we make use of the tool of...